Gierach Gretchen L, Lacey James V, Schatzkin Arthur, Leitzmann Michael F, Richesson Douglas, Hollenbeck Albert R, Brinton Louise A
Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd, Suite 550, Rockville, MD 20852-7234, USA.
Breast Cancer Res. 2008;10(2):R38. doi: 10.1186/bcr2089. Epub 2008 Apr 30.
By inhibiting cyclooxygenase-2, nonsteroidal anti-inflammatory drugs (NSAIDs) decrease aromatase activity and might reduce breast cancer risk by suppressing estrogen synthesis. Epidemiologic evidence for a protective role of NSAIDs in breast cancer, however, is equivocal.
We tested NSAID use for its association with breast cancer incidence in the National Institutes of Health-AARP Diet and Health Study, where 127,383 female AARP (formerly known as the American Association of Retired Persons) members with no history of cancer, aged 51 to 72 years, completed a mailed questionnaire (1996 to 1997). We estimated relative risks of breast cancer for NSAID exposures using multivariate Cox proportional hazards regression models. The state cancer registry and mortality index linkage identified 4,501 primary incident breast cancers through 31 December 2003, including 1,439 estrogen receptor (ER)-positive cancers and 280 ER-negative cancers.
Proportional hazards models revealed no statistically significant association between overall NSAIDs and total breast cancer. As cyclooxygenase inhibition by aspirin (but not other NSAIDs) is irreversible, we tested associations by NSAID type. Although we observed no significant differences in risk for daily use (versus nonuse) of aspirin (relative risk = 0.93, 95% confidence interval = 0.85 to 1.01) or nonaspirin NSAIDS (relative risk = 0.96, 95% confidence interval = 0.87 to 1.05), risk of ER-positive breast cancer was significantly reduced with daily aspirin use (relative risk = 0.84, 95% confidence interval = 0.71 to 0.98)--a relationship not observed for nonaspirin NSAIDS. Neither aspirin nor nonaspirin NSAIDs were associated with risk of ER-negative breast cancer.
Breast cancer risk was not significantly associated with NSAID use, but daily aspirin use was associated with a modest reduction in ER-positive breast cancer. Our results provide support for further evaluating relationships by NSAID type and breast cancer subtype.
通过抑制环氧化酶 - 2，非甾体抗炎药（NSAIDs）可降低芳香化酶活性，并可能通过抑制雌激素合成来降低乳腺癌风险。然而，关于NSAIDs在乳腺癌中具有保护作用的流行病学证据并不明确。
在美国国立卫生研究院 - AARP饮食与健康研究中，我们测试了NSAIDs的使用与乳腺癌发病率之间的关联。该研究中，127383名年龄在51至72岁、无癌症病史的女性AARP（原美国退休人员协会）成员完成了一份邮寄问卷（1996年至1997年）。我们使用多变量Cox比例风险回归模型估计NSAIDs暴露导致乳腺癌的相对风险。通过与州癌症登记处和死亡率指数建立联系，截至2003年12月31日，共识别出4501例原发性乳腺癌病例，其中包括1439例雌激素受体（ER）阳性癌症和280例ER阴性癌症。
比例风险模型显示，总体NSAIDs与乳腺癌总数之间无统计学上的显著关联。由于阿司匹林（而非其他NSAIDs）对环氧化酶的抑制作用是不可逆的，我们按NSAIDs类型测试了关联。尽管我们观察到每日使用阿司匹林（相对于不使用）（相对风险 = 0.93，95%置信区间 = 0.85至1.01）或非阿司匹林NSAIDs（相对风险 = 0.96，95%置信区间 = 0.87至1.05）的风险无显著差异，但每日使用阿司匹林可使ER阳性乳腺癌的风险显著降低（相对风险 = 0.84，95%置信区间 = 0.71至0.98）——非阿司匹林NSAIDs未观察到这种关系。阿司匹林和非阿司匹林NSAIDs均与ER阴性乳腺癌的风险无关。
乳腺癌风险与NSAIDs的使用无显著关联，但每日使用阿司匹林与ER阳性乳腺癌风险适度降低有关。我们的结果为进一步按NSAIDs类型和乳腺癌亚型评估两者关系提供了支持。
